The hippocampus is a highly plastic brain structure that plays a central role in cognition, memory, learning and spatial location. As such, this brain structure, which is sensitive to ageing, is generally considered to be the main target of Alzheimer’s disease features: neurofibrillary tangles, amyloid plaques and neuronal loss. Structural brain MRI measures a decrease in hippocampal volume associated with local neuronal and synaptic loss.
This brain biomarker is widely used clinically for diagnosis and prognosis, but also in research as an early and surrogate biomarker, notably for including subjects at risk of Alzheimer’s disease in studies to assess the effect of early treatments.
To assess the predictive power of a hippocampal measurement on the risk of developing Alzheimer’s disease, Sylvaine Artero and Mélissa Gentreau conducted a study on 510 people aged 65 and over who underwent brain MRI as part of the Esprit study, 42 of whom developed dementia. Participants from general population were followed for 15 years to assess their cognitive abilities over the very long term, and whether hippocampal volume could be a relevant early biomarker of cognitive decline.
The study showed that a reduced hippocampal volume not only predicted the onset of Alzheimer’s disease, but also mild cognitive impairment in people who would never develop dementia. This study thus suggests for the first time that the use of an isolated measure of the hippocampus may not be highly relevant for early detection of only people at risk of dementia, and thus potentially bias some clinical studies. These findings may be explained by the fact that hippocampal volume, and the neurogenesis that exists in this area, may be sensitive to many potentially modifiable factors such as poor diet, physical inactivity, obesity, air pollution, sleep disorders, stress and depression. This study also highlights the differences in results between manual and automatic hippocampal measurements.
Thus, this work raises the question of the relevance of hippocampal measurement as an early marker of dementia in the general population, and its usefulness for including patients in clinical studies. But the results also suggest that all people with a reduced hippocampus should benefit from targeted preventive measures to slow or prevent the cognitive decline that impairs quality of life and autonomy in the elderly.
